The evaluation of the biologic implications of hormone response potential in malignant as well as beningn and dysplastic lesions of the human mammary gland have been hampered by technological difficulties relating to the heterogeneity of the human breast and its disorders. The development of an effective immunocytochemical techniques for the evaluation of at least one step in the pathway of sex steroid action makes possible the study of the tissue components contributing to the tissue reponse potential and/or degree of tissue differentiation. The present projectg proposes to use a monoclonal antibody directed against estrogen receptor (H222) on material which has been collected over the past eight years and stored at -80 C from over 1000 cases which have been carefully characterized clinically at the time of the surgical resection of the tissue and with follow-up of the clinical course of these patients thorugh periods up to 8 years. The pattern of localization of H222 method will be compared to menstrual cycle data for primary tumors, beningn and dysplastic lesions, and to clinical response to hormone therapy for metastatic disease. The prognostic significance of the pattern of localization of such antigentically defined estrogen receptor will be tested by analyses of material from primary breast cancers with follow-up from initial resection to disease recurrence for disease free interval and survival with a follow-up period of a minimum of five years. The overall goal of this project will be to establish whether heterogeneity in distribution of antigentically defined receptor in comparison to the biochemical quantitation of estrogen and progesterone receptor carries additional biologically significant and prognostic information. The comparison of apparent receptor heterogeneity with elements of the tumor with different histology will serve to evaluate if components of a tumor are associated with greater propensity to demonstrate the receptor protein and whether this information carries additional prognostic information beyond quantitative receptor analysis or tumor grade alone, controlling for tumor stage.